Synthesis and biological evaluation of novel substituted pyrrolo[1,2-a]quinoxaline derivatives as inhibitors of the human protein kinase CK2

Autores
Guillon, Jean; Le Borgne, Marc; Rimbault, Charlotte; Moreau, Stéphane; Savrimoutou, Solène; Pinaud, Noël; Baratin, Sophie; Marchivie, Mathieu; Roche, Séverine; Bollacke, Andre; Pecci, Adali; Alvarez, Lautaro Damian; Desplat, Vanessa; Joachim, Jose
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Herein we describe the synthesis and properties of substituted phenylaminopyrrolo[1,2-a]quinoxaline-carboxylic acid derivatives as a novel class of potent inhibitors of the human protein kinase CK2. A set of 15 compounds was designed and synthesized using convenient and straightforward synthesis protocols. The compounds were tested for inhibition of human protein kinase CK2, which is a potential drug target for many diseases including inflammatory disorders and cancer. New inhibitors with IC50 in the micro- and sub-micromolar range were identified. The most promising compound, the 4-[(3-chlorophenyl)amino]pyrrolo[1,2-a]quinoxaline-3-carboxylic acid 1c inhibited human CK2 with an IC50 of 49 nM. Our findings indicate that pyrrolo[1,2-a]quinoxalines are a promising starting scaffold for further development and optimization of human protein kinase CK2 inhibitors
Fil: Guillon, Jean. Université de Bordeaux; Francia
Fil: Le Borgne, Marc. Université de Lyon; Francia
Fil: Rimbault, Charlotte. Université de Bordeaux; Francia
Fil: Moreau, Stéphane. Université de Bordeaux; Francia
Fil: Savrimoutou, Solène. Université de Bordeaux; Francia
Fil: Pinaud, Noël. Université de Bordeaux; Francia
Fil: Baratin, Sophie. Université de Bordeaux; Francia
Fil: Marchivie, Mathieu. Université de Bordeaux; Francia
Fil: Roche, Séverine. Université de Bordeaux; Francia
Fil: Bollacke, Andre. Institut für Pharmazeutische und Medizinische Chemie. Westfälische Wilhelms-Universität Münster; Alemania; Andorra
Fil: Pecci, Adali. Consejo Nacional de Invest.cientif.y Tecnicas. Oficina de Coordinacion Administrativa Ciudad Universitaria. Instituto de Fisiol., Biol.molecular y Neurociencias; Argentina
Fil: Alvarez, Lautaro Damian. Consejo Nacional de Invest.cientif.y Tecnicas. Oficina de Coordinacion Administrativa Ciudad Universitaria. Unid.microanal.y Met.fisicos En Quim.org.(i); . Universidad de Buenos Aires. Facultad de Cs.exactas y Naturales. Departamento de Quimica Organica;
Fil: Desplat, Vanessa. Université de Bordeaux; Francia
Fil: Joachim, Jose. Institut für Pharmazeutische und Medizinische Chemie. Westfälische Wilhelms-Universität Münster; Alemania
Materia
Antiproliferative Activity
Protein Kinase Ck2
Pyrrolo[1,2-A]Quinoxaline
Molecula Modeling
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/758
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/758
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Synthesis and biological evaluation of novel substituted pyrrolo[1,2-a]quinoxaline derivatives as inhibitors of the human protein kinase CK2Guillon, JeanLe Borgne, MarcRimbault, CharlotteMoreau, StéphaneSavrimoutou, SolènePinaud, NoëlBaratin, SophieMarchivie, MathieuRoche, SéverineBollacke, AndrePecci, AdaliAlvarez, Lautaro DamianDesplat, VanessaJoachim, JoseAntiproliferative ActivityProtein Kinase Ck2Pyrrolo[1,2-A]QuinoxalineMolecula Modelinghttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Herein we describe the synthesis and properties of substituted phenylaminopyrrolo[1,2-a]quinoxaline-carboxylic acid derivatives as a novel class of potent inhibitors of the human protein kinase CK2. A set of 15 compounds was designed and synthesized using convenient and straightforward synthesis protocols. The compounds were tested for inhibition of human protein kinase CK2, which is a potential drug target for many diseases including inflammatory disorders and cancer. New inhibitors with IC50 in the micro- and sub-micromolar range were identified. The most promising compound, the 4-[(3-chlorophenyl)amino]pyrrolo[1,2-a]quinoxaline-3-carboxylic acid 1c inhibited human CK2 with an IC50 of 49 nM. Our findings indicate that pyrrolo[1,2-a]quinoxalines are a promising starting scaffold for further development and optimization of human protein kinase CK2 inhibitorsFil: Guillon, Jean. Université de Bordeaux; FranciaFil: Le Borgne, Marc. Université de Lyon; FranciaFil: Rimbault, Charlotte. Université de Bordeaux; FranciaFil: Moreau, Stéphane. Université de Bordeaux; FranciaFil: Savrimoutou, Solène. Université de Bordeaux; FranciaFil: Pinaud, Noël. Université de Bordeaux; FranciaFil: Baratin, Sophie. Université de Bordeaux; FranciaFil: Marchivie, Mathieu. Université de Bordeaux; FranciaFil: Roche, Séverine. Université de Bordeaux; FranciaFil: Bollacke, Andre. Institut für Pharmazeutische und Medizinische Chemie. Westfälische Wilhelms-Universität Münster; Alemania; AndorraFil: Pecci, Adali. Consejo Nacional de Invest.cientif.y Tecnicas. Oficina de Coordinacion Administrativa Ciudad Universitaria. Instituto de Fisiol., Biol.molecular y Neurociencias; ArgentinaFil: Alvarez, Lautaro Damian. Consejo Nacional de Invest.cientif.y Tecnicas. Oficina de Coordinacion Administrativa Ciudad Universitaria. Unid.microanal.y Met.fisicos En Quim.org.(i); . Universidad de Buenos Aires. Facultad de Cs.exactas y Naturales. Departamento de Quimica Organica;Fil: Desplat, Vanessa. Université de Bordeaux; FranciaFil: Joachim, Jose. Institut für Pharmazeutische und Medizinische Chemie. Westfälische Wilhelms-Universität Münster; AlemaniaElsevier France-editions Scientifiques Medicales Elsevier2013-07info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/758Guillon, Jean; Le Borgne, Marc; Rimbault, Charlotte; Moreau, Stéphane; Savrimoutou, Solène; et al.; Synthesis and biological evaluation of novel substituted pyrrolo[1,2-a]quinoxaline derivatives as inhibitors of the human protein kinase CK2; Elsevier France-editions Scientifiques Medicales Elsevier; European Journal Of Medical Chemistry; 65; 7-2013; 205-2220223-5234enginfo:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0223523413002833info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:56:43Zoai:ri.conicet.gov.ar:11336/758instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 09:56:44.244CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Synthesis and biological evaluation of novel substituted pyrrolo[1,2-a]quinoxaline derivatives as inhibitors of the human protein kinase CK2
title Synthesis and biological evaluation of novel substituted pyrrolo[1,2-a]quinoxaline derivatives as inhibitors of the human protein kinase CK2
spellingShingle Synthesis and biological evaluation of novel substituted pyrrolo[1,2-a]quinoxaline derivatives as inhibitors of the human protein kinase CK2
Guillon, Jean
Antiproliferative Activity
Protein Kinase Ck2
Pyrrolo[1,2-A]Quinoxaline
Molecula Modeling
title_short Synthesis and biological evaluation of novel substituted pyrrolo[1,2-a]quinoxaline derivatives as inhibitors of the human protein kinase CK2
title_full Synthesis and biological evaluation of novel substituted pyrrolo[1,2-a]quinoxaline derivatives as inhibitors of the human protein kinase CK2
title_fullStr Synthesis and biological evaluation of novel substituted pyrrolo[1,2-a]quinoxaline derivatives as inhibitors of the human protein kinase CK2
title_full_unstemmed Synthesis and biological evaluation of novel substituted pyrrolo[1,2-a]quinoxaline derivatives as inhibitors of the human protein kinase CK2
title_sort Synthesis and biological evaluation of novel substituted pyrrolo[1,2-a]quinoxaline derivatives as inhibitors of the human protein kinase CK2
dc.creator.none.fl_str_mv Guillon, Jean
Le Borgne, Marc
Rimbault, Charlotte
Moreau, Stéphane
Savrimoutou, Solène
Pinaud, Noël
Baratin, Sophie
Marchivie, Mathieu
Roche, Séverine
Bollacke, Andre
Pecci, Adali
Alvarez, Lautaro Damian
Desplat, Vanessa
Joachim, Jose
author Guillon, Jean
author_facet Guillon, Jean
Le Borgne, Marc
Rimbault, Charlotte
Moreau, Stéphane
Savrimoutou, Solène
Pinaud, Noël
Baratin, Sophie
Marchivie, Mathieu
Roche, Séverine
Bollacke, Andre
Pecci, Adali
Alvarez, Lautaro Damian
Desplat, Vanessa
Joachim, Jose
author_role author
author2 Le Borgne, Marc
Rimbault, Charlotte
Moreau, Stéphane
Savrimoutou, Solène
Pinaud, Noël
Baratin, Sophie
Marchivie, Mathieu
Roche, Séverine
Bollacke, Andre
Pecci, Adali
Alvarez, Lautaro Damian
Desplat, Vanessa
Joachim, Jose
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Antiproliferative Activity
Protein Kinase Ck2
Pyrrolo[1,2-A]Quinoxaline
Molecula Modeling
topic Antiproliferative Activity
Protein Kinase Ck2
Pyrrolo[1,2-A]Quinoxaline
Molecula Modeling
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Herein we describe the synthesis and properties of substituted phenylaminopyrrolo[1,2-a]quinoxaline-carboxylic acid derivatives as a novel class of potent inhibitors of the human protein kinase CK2. A set of 15 compounds was designed and synthesized using convenient and straightforward synthesis protocols. The compounds were tested for inhibition of human protein kinase CK2, which is a potential drug target for many diseases including inflammatory disorders and cancer. New inhibitors with IC50 in the micro- and sub-micromolar range were identified. The most promising compound, the 4-[(3-chlorophenyl)amino]pyrrolo[1,2-a]quinoxaline-3-carboxylic acid 1c inhibited human CK2 with an IC50 of 49 nM. Our findings indicate that pyrrolo[1,2-a]quinoxalines are a promising starting scaffold for further development and optimization of human protein kinase CK2 inhibitors
Fil: Guillon, Jean. Université de Bordeaux; Francia
Fil: Le Borgne, Marc. Université de Lyon; Francia
Fil: Rimbault, Charlotte. Université de Bordeaux; Francia
Fil: Moreau, Stéphane. Université de Bordeaux; Francia
Fil: Savrimoutou, Solène. Université de Bordeaux; Francia
Fil: Pinaud, Noël. Université de Bordeaux; Francia
Fil: Baratin, Sophie. Université de Bordeaux; Francia
Fil: Marchivie, Mathieu. Université de Bordeaux; Francia
Fil: Roche, Séverine. Université de Bordeaux; Francia
Fil: Bollacke, Andre. Institut für Pharmazeutische und Medizinische Chemie. Westfälische Wilhelms-Universität Münster; Alemania; Andorra
Fil: Pecci, Adali. Consejo Nacional de Invest.cientif.y Tecnicas. Oficina de Coordinacion Administrativa Ciudad Universitaria. Instituto de Fisiol., Biol.molecular y Neurociencias; Argentina
Fil: Alvarez, Lautaro Damian. Consejo Nacional de Invest.cientif.y Tecnicas. Oficina de Coordinacion Administrativa Ciudad Universitaria. Unid.microanal.y Met.fisicos En Quim.org.(i); . Universidad de Buenos Aires. Facultad de Cs.exactas y Naturales. Departamento de Quimica Organica;
Fil: Desplat, Vanessa. Université de Bordeaux; Francia
Fil: Joachim, Jose. Institut für Pharmazeutische und Medizinische Chemie. Westfälische Wilhelms-Universität Münster; Alemania
description Herein we describe the synthesis and properties of substituted phenylaminopyrrolo[1,2-a]quinoxaline-carboxylic acid derivatives as a novel class of potent inhibitors of the human protein kinase CK2. A set of 15 compounds was designed and synthesized using convenient and straightforward synthesis protocols. The compounds were tested for inhibition of human protein kinase CK2, which is a potential drug target for many diseases including inflammatory disorders and cancer. New inhibitors with IC50 in the micro- and sub-micromolar range were identified. The most promising compound, the 4-[(3-chlorophenyl)amino]pyrrolo[1,2-a]quinoxaline-3-carboxylic acid 1c inhibited human CK2 with an IC50 of 49 nM. Our findings indicate that pyrrolo[1,2-a]quinoxalines are a promising starting scaffold for further development and optimization of human protein kinase CK2 inhibitors
publishDate 2013
dc.date.none.fl_str_mv 2013-07
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/758
Guillon, Jean; Le Borgne, Marc; Rimbault, Charlotte; Moreau, Stéphane; Savrimoutou, Solène; et al.; Synthesis and biological evaluation of novel substituted pyrrolo[1,2-a]quinoxaline derivatives as inhibitors of the human protein kinase CK2; Elsevier France-editions Scientifiques Medicales Elsevier; European Journal Of Medical Chemistry; 65; 7-2013; 205-222
0223-5234
url http://hdl.handle.net/11336/758
identifier_str_mv Guillon, Jean; Le Borgne, Marc; Rimbault, Charlotte; Moreau, Stéphane; Savrimoutou, Solène; et al.; Synthesis and biological evaluation of novel substituted pyrrolo[1,2-a]quinoxaline derivatives as inhibitors of the human protein kinase CK2; Elsevier France-editions Scientifiques Medicales Elsevier; European Journal Of Medical Chemistry; 65; 7-2013; 205-222
0223-5234
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0223523413002833
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier France-editions Scientifiques Medicales Elsevier
publisher.none.fl_str_mv Elsevier France-editions Scientifiques Medicales Elsevier
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.070432

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